Coronary Care Unit, "O.Barberi", "G.F.Ingrassia" Hospital, Palermo, Italy.
Department Cardiology "Paolo Borsellino", "G.F.Ingrassia" Hospital, Corso Calatafimi 1002, 90100, Palermo, Italy.
J Thromb Thrombolysis. 2018 May;45(4):588-592. doi: 10.1007/s11239-018-1624-3.
This case report describes agranulocytosis immediately after oral administration of dabigatran in a 68 years old man with atrial fibrillation (AF). Dabigatran is an oral, reversible and competitive thrombin inhibitor that has shown promising results. In patients with atrial fibrillation of RE-LY study (Randomized Evaluation of Long-Term Anticoagulant Therapy), dabigatran administered at a dose of 150 mg, as compared with warfarin, was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage. Dabigatran is administered as a prodrug and the peak of the plasma concentrations occurs within 2 h of ingestion. Agranulocytosis is characterized by a severe decrease or lack of circulating granulocytes. This rare event can be found among people taking dabigratan, especially for people who are female, over the age of 60, who took the drug for < 1 month. Agranulocytosis and aplastic anaemia are rare but serious conditions known to be caused by numerous drugs. Most of what is known or suspected about the aetiology is based on case reports, with only a few formal epidemiological studies that provide quantitative estimates of risk. The patient's white blood cell count increased abruptly after discontinuation of the drug, suggesting an immune response caused by dabigatran. Although anticoagulant drugs are commonly used to treat atrial fibrillation, attention should be paid to this aspect and possible drug interactions.
本病例报告描述了一名 68 岁房颤(AF)患者在口服达比加群后立即出现粒细胞缺乏症。达比加群是一种口服、可逆和竞争性的凝血酶抑制剂,已显示出良好的效果。在房颤的 RE-LY 研究(随机评价长期抗凝治疗)中,与华法林相比,达比加群 150mg 剂量组的卒中及全身性栓塞发生率较低,但大出血发生率相似。达比加群作为前体药物给药,其血浆浓度峰值在摄入后 2 小时内出现。粒细胞缺乏症的特征是循环粒细胞严重减少或缺乏。这种罕见的事件可能发生在服用达比加群的人群中,尤其是女性、年龄超过 60 岁、服用药物<1 个月的人群。粒细胞缺乏症和再生障碍性贫血虽然罕见,但却是由许多药物引起的严重疾病。关于病因学的大多数已知或可疑的信息都是基于病例报告,只有少数正式的流行病学研究提供了风险的定量估计。患者在停药后白细胞计数突然升高,提示达比加群引起的免疫反应。虽然抗凝药物常用于治疗房颤,但应注意这一方面及可能的药物相互作用。